Results were sensitive to the prevalence of H. pylori in DU (base=95%). Urease-based testing was preferred below an H. pylori prevalence of 66% (rare except in a population where NSAID use is high).

Comment

An interesting simulation and analytic evaluation that needed to be done. The study provides good evidence that H2RA therapy alone for DU is passe. This result came through despite several biases against HpRx treatment (e.g., duration of analysis was short, only 1 year, precluding the occurrence of more and multiple DU recurrences with H2RA alone and the natural history of DU was not included and avoided additional costs of recurrent DU). One bias toward HpRx was the absence of amoxicillin/omperazole combination which has a risk, albeit low, of C.
difficile and amoxicillin-induced diarrhea with additional costs for stool studies.

I think we'll see additional cost-effectiveness analyses on this subject. They should avoid several problems highlighted in this study:

1) there is no need to consider H2RA but, rather, the mode of
evaluation and treatment for someone with peptic symptoms should be modeled,
2) the natural history of DU should also be modeled,
3) extend the model beyond one year to capture the cost
of multiple recurrences, and
4) use quality-adjusted life years (QALYS) as an outcome rather
than cost per cure to allow comparison to other medical interventions.

Additionally, several errors missed by reviewers:

1) Table 3 used average cost versus marginal cost which inflates the true cost per cure.
2) Figure 2 is a one-way sensitivity analysis not two-way (only variable modified is prevalence since cost per cure is an outcome, not an independent variable).
3) Figure 3 does not label outcome being compared (e.g., cures vs cost per cure).

Comments (by Michael Jacobson)

This article is a good example of decision analysis / cost analysis. It is a technique applicable in a situation where there are several possible strategic approaches to a problem, each with a number of possible outcomes. It requires knowledge or estimation of the probability of each outcome as well as estimation of the cost associated with each outcome and strategy. The basic technique, as illustrated in the article, involves four steps:

1) construction of a decision tree that explicitly shows each possible strategic choice and possible outcome (see Fig. 1 in the article).
2) assignment of a probability to each outcome (based on review of the literature or other source of knowledge) and a $ cost for each procedure or outcome (based on reasonable cost estimates from various sources).
3) once all of this knowledge is entered into the decision tree, a computer analysis is done, which yields the estimated average cost for each possible strategy, and thus determines a most cost-effective strategy. Obviously, this determination will depend on each of the assumptions about probability and cost that have been made, thus, an important fourth step is:
4) a sensitivity analysis, where the results are recalculated, varying the previously determined parameters (cost and probability) within reasonable limits, to see if the most cost-effective choice remains the same within all reasonable limits of the parameters.

In this article, the most cost-effective initial approach to treating endoscopically documented duodenal ulcer turned out to be treatment with H. pylori antibiotics (triple therapy with amoxicillin, metronidazole and bismuth subsalicylate) plus H2 receptor antagonists. This is not surprising, considering that the authors decided to assume that patients had
no other known risk factors for DU, and thus that the prevalence of H. pylori would be extremely high (95% in their estimate).

As Dr. Bennett points out, it will be more interesting to see what such a cost analysis shows for the frequent patient presenting with dyspepsia. Is endoscopy the most cost-effective approach?

In my opinion, a very real benefit of working through this not-so-easy article is to understand how such an analysis is performed, since it will certainly be seen frequently in the medical literature in the years to come.

Reader comments

As a practicing primary care provider in the U.S. these cost analyses seem to
skip too many steps to me. I may have missed part of the information
provided, and any clarification would be appreciated.

As I understand it, H. pylori eradication is clearly indicated for patients
with documented duodenal (and probably gastric) ulcer but not for patients
with simple dyspepsia or dyspepsia/gastritis. H2 blockers do seem helpful
for non-ulcer dyspepsia, although perhaps only as placebo.

For the patient, younger than 50, presenting with symptoms of dyspepsia, it
seems to me I have 3 choices: treat empirically for non-ulcer dyspepsia with
H2 blockers, treat empirically for ulcer with H. pylori eradication, or do a
diagnostic procedure (UGI series or endoscopy). For cost and comfort
reasons, my patients are reluctantant to pursue diagnosis and I find compelled
to do so only in patients with risk of malignancy. But then which treatment
course to pursue? Most cost analysis seems to occur after diagnostic endoscopy
and not place this procedure into the equation. Any further perspectives or
strategies?

As you note, this study only provides guidance for treating endoscopically documented ulcer disease. The question of the most cost-effective treatment for non-endoscoped dyspepsia is left entirely open by this analysis, and will need to be addressed. Is endoscopy the initial strategy of choice, or is empiric therapy the best first approach? Obviously, this will depend on the patient population and risk of malignancy. And if empiric therapy is to be undertaken first, which one?

Although only more studies/analyses can answer these questions, one point can be made based on the current study: urease testing prior to therapy with H. Pylori antibiotics was only slightly more expensive than empiric therapy alone, and only as long as the prevalence of H. Pylori was greater than 66%. Looking at all-comers with dyspepsia, the prevalence of H. Pylori is likely to be much lower than the 95% (assumed by the authors) in patients with documented duodenal ulcer. Thus, empiric treatment with antibiotics in addition to H2 blockers for symptoms of dyspepsia does not seem to be justified. Whether urease-test-based antibiotic therapy for H Pylori is a reasonable approach cannot be answered from the data presented here.

The authors themselves, in their discussion, state: "Because we assume in this model that duodenal ulcer disease is diagnosed by endoscopy, the results do not apply to patients with suspected ulcer disease or dyspepsia ..."-- mj